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The therapeutic candidate for immune checkpoint inhibitors elucidated by the status of tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) expression in triple negative breast cancer (TNBC)

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Abstract

Background

The status of tumor-infiltrating lymphocytes (TILs) is a prognostic factor for triple negative breast cancer (TNBC). Recent studies have shown that programmed cell death 1 (PD-1) or programmed death ligand 1 (PD-L1) is expressed on T lymphocytes or tumor cells modulating antitumor immunity. The regulation of immune checkpoints between tumor cells and T lymphocytes may serve as a target for improvement of TNBC prognosis. We investigated TILs and PD-L1 status in TNBCs before or after preoperative systemic therapy (PST) to elucidate the clinical significance of PD-L1 expression.

Methods

Ninety patients received PST, and materials of core needle biopsies (CNB) taken before PST were available for 32 patients. TILs were scored as “% stromal”, and tumors were defined as High-TILs (≥30%) or Low-TILs (<30%). The expression of PD-L1 was assessed by immunohistochemistry.

Results

TILs status in CNB is significant in pathological therapeutic grade: 1 vs. 2 or 3 (p = 0.0359). Disease-free survival (DFS) in patients with Low-TIL tumors were significantly worse than those with High-TIL tumors (p = 0.0383), but overall survival (OS) showed no significance (p = 0.0772). However, in patients with Low-TIL tumors, both DFS and OS in patients with High-PD-L1 expression were extremely unfavorable than in patients with Low-PD-L1 expression (p = 0.0032, p = 0.0002).

Conclusion

The patients with TNBCs with combined Low-TILs and High-PD-L1 status in pre-PST situation showed unfavorable prognosis. The subset of TNBCs with Low-TILs and High-PD-L1 status could be the therapeutic target for immune checkpoint inhibitor.

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Acknowledgements

We thank the patients, their families, and the study personnel across all sites for participating in this study.

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Authors and Affiliations

  1. Department of Breast Surgery, National Hospital Organization (NHO) Hokkaido Cancer Center, 4-2 Kikusui, Shiroishi-ku, Sapporo, 003-0804, Japan

    Nobumoto Tomioka, Mitsugu Yamamoto, Masako Sato, Ken-ichi Watanabe & Masato Takahashi

  2. Department of Clinical Pathology, National Hospital Organization (NHO) Hokkaido Cancer Center, 4-2 Kikusui, Shiroishi-ku, Sapporo, 003-0804, Japan

    Manabu Azuma & Katsushige Yamashiro

  3. Division of Digestive and General Surgery, Niigata University, 1-757 Asahimachi-dori, chuou-ku, Niigata, 951-8510, Japan

    Mayuko Ikarashi

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  1. Nobumoto Tomioka
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  2. Manabu Azuma
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Correspondence to Masato Takahashi.

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Tomioka, N., Azuma, M., Ikarashi, M. et al. The therapeutic candidate for immune checkpoint inhibitors elucidated by the status of tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) expression in triple negative breast cancer (TNBC). Breast Cancer 25, 34–42 (2018). https://doi.org/10.1007/s12282-017-0781-0

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  • DOI: https://doi.org/10.1007/s12282-017-0781-0

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